Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 22, Pages -Publisher
MDPI
DOI: 10.3390/ijms222212304
Keywords
olfactory receptor (OR); all-trans retinoic acid (ATRA); cell proliferation; calcium influx; G-protein-coupled receptor (GPCR); overexpression
Funding
- National Research Foundation of Korea - Korean government (MSIT) [2020R1C1C1010303]
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science and Technology Information and Communication [2020R1F1A1067731]
- National Research Foundation of Korea [2020R1F1A1067731, 2020R1C1C1010303] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Olfactory receptor OR7A17 plays a role in the ATRA-induced suppression of human keratinocyte proliferation, regulated through retinoic acid receptor signaling. Overexpression of OR7A17 can reverse the ATRA-induced attenuation of Ca2+ entry.
Olfactory receptors (ORs), which belong to the G-protein-coupled receptor family, have been widely studied as ectopically expressed receptors in various human tissues, including the skin. However, the physiological functions of only a few OR types have been elucidated in skin cells. All-trans retinoic acid (ATRA) is a well-known medication for various skin diseases. However, many studies have shown that ATRA can have adverse effects, resulting from the suppression of cell proliferation. Here, we investigated the involvement of OR7A17 in the ATRA-induced suppression of human keratinocyte (HaCaT) proliferation. We demonstrated that OR7A17 is expressed in HaCaT keratinocytes, and its expression was downregulated by ATRA. The ATRA-induced downregulation of OR7A17 was attenuated via RAR alpha or RAR gamma antagonist treatment, indicating that the effects of ATRA on OR7A17 expression were mediated through nuclear retinoic acid receptor signaling. Moreover, we found that the overexpression of OR7A17 induced the proliferation of HaCaT cells while counteracting the antiproliferative effect of ATRA. Mechanistically, OR7A17 overexpression reversed the ATRA-induced attenuation of Ca2+ entry. Our findings indicated that ATRA suppresses cell proliferation through the downregulation of OR7A17 via RAR alpha- and gamma-mediated retinoid signaling. Taken together, OR7A17 is a potential therapeutic target for ameliorating the anti-proliferative effects of ATRA.
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